1. Field of the Invention
The present invention is directed to pharmaceutical compositions which have adrenergic effects, and which comprise as active ingredients one or more 2-(2-alkyl-phenylamino)-oxazoline, 2-(2-alkylphenylamino)-thiazoline or 2-(2-alkylphenylamino)imidazoline compounds. The pharmaceutical compositions are useful for treating or preventing conditions in animals of the mammalian species which normally respond to treatment by adrenergic agents. Thus, the pharmaceutical compositions of the inventions are useful as agents for altering the rate of fluid flow in the gastrointestinal tract (anti-diarrhetic), anti-spastic, anti-hypertensive, anti-ischemic, anti-epileptic, agents for increasing fluid flow in at least one kidney (diuretic) anesthetic, memory-enhancing agents and as sleeping aids. In another aspect, the present invention is directed to administering such formulations and compositions to animals of the mammalian species (including humans) for treating the above-noted diseases and conditions.
2. Brief Description of Background Art
Adrenergic agents, and particularly agents affective on .alpha..sub.2 adrenergic receptors are known in the art. For example, U.S. Pat. No. 5,091,528 describes 6- or 7-(2-imino-2-imidazolidine)-1,4-benzoxazines as .alpha. adrenergic agents. Published European Patent Application 0 251 453 describes certain cyclohexyl substituted amino-dihydro-oxazoles, -thiazoles and -imidazoles as .alpha..sub.2 adrenergic agents. U.S. Pat. No. 3,598,833 describes 2-cycloalkylamino oxazolines having local anesthetic, sedative, vasoconstrictory, mucous membrane deswelling, blood pressure depressant and gastric fluid secretion inhibitory effects. Further United States and foreign patents and scientific publications which pertain to substituted amino-oxazolines, imidazolines and thiazolines are as follows:
U.S. Pat. No. 4,587,257 [2-(trisubstituted phenylimino)imidazoline compounds capable of controlling ocular bleeding];
U.S. Pat. No. 3,636,219 [2-(substituted-phenylamino)-thiazolines and imidazolines having anticholinergic activity];
U.S. Pat. No. 3,453,284 [2-(substituted-anilino)-2-oxazolines;
U.S. Pat. No. 3,432,600 [partially reduced 2-(naphtylamino) oxazolines and indanylamino oxazolines;
U.S. Pat. No. 3,679,798 [compositions comprising arylaminooxazolines and an antocholigeneric agent];
U.S. Pat. No. 3,624,092 [aminooxazolines useful as central nervous system depressants];
U.S. Pat. No. 2,876,232 [2-(9-fluorenylamino)-oxazolines,) and German Patent Nos. 1,191,381 and 1,195,323, and European Patent Application No. 87304019.0.
U.S. Pat. No. 4,515,800 [2-(trisubstituted phenylimino) imidazoline compounds, also known as 2- (trisubstituted-anilino)-1,3-diazacyclopentene-(2) compounds, treatment of glaucoma].
U.S. Pat. No. 5,066,664 [2-(hydroxy-2-alkylphenylamino)-oxazolines and thiazolines, anti-glaucoma and vasoconstrictive agents].
Chapleo et al. in Journal of Medicinal Chemistry, 1989 32, 1627-1630 describe heteroaromatic analogues of clonidine as partial agonists of .alpha..sub.2 adrenoreceptor.
U.S. Pat. No. 5,151,440 describes ophthalmic compositions suitable for lowering intraocular pressure, comprising compounds of substantially the same structure as the compounds used as adrenergic agents in the present invention.
As it will become apparent from the ensuing description, some of the "composition of matter" used in the novel pharmaceutical compositions and methods of administration of the present invention are described or mentioned in one or more of the above-listed references, but the activity of these compounds as adrenergic agents, and especially as agents acting on the .alpha..sub.2 adrenergic receptor is believed to be novel to the present invention.